The undesirable properties of nucleoside analogs can be avoided and selective effects on disease states realized by utilization of conformational principles currently being established. The effects of adenosine on cAMP mediated control of diseased or normal metabolism can be selectively manipulated through application of conformational principles. Our research interests include the following: 1. The conformational and structural properties controlling the formation of 5-phosphoribosyl l-pyrophosphate (PRPP). 2. The role of enzymes such as 5'-nuleotidase that form adenosine from adenosine-5'-phosphate. 3. The imputed control of cellular metabolism by cAMP or cGMP may have a more fundamental basis. Cellular activities may be controlled through the coordinated effects of nucleotides on PRPP and adenosine formation. The conformational properties of nucleoside and nucleotide analogs form the basis for understanding the control of biological activities. Adenosine is involved in a wide variety of biological mechanisms, many of which are mediated by cAMP. The effect of adenosine on the heart rate and blood pressure appears to be controlled by the relative stabilities of the anti and high anti glycosidic conformations required by cardiac receptors. Adenosine analogs may be designed to lower blood pressure without decreasing the heart rate if the conformational basis for these effects are utilized. BIBLIOGRAPHIC REFERENCES: "Electronic Absorption and Magnetic Circular Dichroism Spectra of Ferrocene" by Dennis Nielson, Morris Farmer, and Henry Eyring, J. Phys. Chem. 80, 717 (1976). "Magnetic Circular Dichroism of Molecules in Dense Media: Spin-forbidden transitions of carbonyl molecules," by Y.H. Yoon, S. T. Lee, S.H.Lin, and H. Eyring, Proc. Natl. Acad. Sci. 73, 2964 (1976).